PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE (PACAP) AND VASOACTIVE-INTESTINAL-PEPTIDE (VIP) STIMULATE INTERLEUKIN-6 PRODUCTION THROUGH THE 3RD SUBTYPE OF PACAP VIP RECEPTOR IN RAT BONE-MARROW-DERIVED STROMAL CELLS/

Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-deri ved stromal cells by neuropeptides, pituitary adenylate cyclase activa ting polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP s ignificantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The th ree related peptides (PACAP-27, -38, and VIP) stimulated the productio n of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat PM-derive d stromal cells with similar 50% effective concentrations. The stimula tory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signali ng transduction pathways may be involved in PACAP/VIP-induced IL-6 pro duction in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both PM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVRB) was detected. F urthermore, the mRNAs for PACAP and VIP were detected in the BM tissue , suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in t he BM. The results shown in this paper suggest that PACAP/VIP and thei r receptor play an important role in the IL-6 production and perhaps i n the hematopoiesis in the BM.